MAP kinases are a large family of pleiotropic protein kinases that transduce signals leading to diverse regulatory events, including proliferation, differentiated functions, and responses to environmental insult. The MAP kinases ERK1 and ERK2 respond to signals leading to growth and differentiation. The related MAP kinase p38 and other homologs are involved in stress responses. MAP kinase family members each have a unique constellation of interactions with substrates and upstream activators that assure faithful signaling. We previously determined the structures of the low activity forms of ERK2 and p38, and the active form of ERK2. We will continue our structural studies of this family, and will analyze the interactions of MAP kinases with peptides and full-length proteins to determine the structural basis for selective interactions of the MAP kinases ERK2 and p38 toward transcription factors and protein kinase substrates. We discovered that ERK2 dimerizes when phosphorylated, and the structure of active ERK2 revealed a dimer. Many MAP kinase substrates are dimers. Dimerization is ubiquitous in signaling processes, and may contribute significantly to correct targeting of signals by improving selectivity for the correct substrates. In this study, we will carry out kinetic analysis of active dimeric ERK2 and an active dimerization- deficient mutant to determine the effect of dimerization on the activity toward transcription factor substrates.